Efficient Inhibition of Human Colorectal Carcinoma Growth by RNA Interference Targeting Polo-Like Kinase 1 In Vitro and In Vivo

被引:12
作者
Xu, Wen-Jing [1 ,2 ,3 ,4 ]
Zhang, Shuang [1 ,2 ]
Yang, Yang [1 ,2 ]
Zhang, Na [1 ,2 ]
Wang, Wei [1 ,2 ]
Liu, Sheng-Yong [1 ,2 ]
Tian, Hong-Wei [1 ,2 ]
Dai, Lei [1 ,2 ]
Xie, Qian [1 ,2 ]
Zhao, Xia [5 ]
Wei, Yu-Quan [1 ,2 ]
Deng, Hong-Xin [1 ,2 ]
机构
[1] Sichuan Univ, State Key Lab Biotherapy, W China Hosp, Chengdu 610041, Sichuan, Peoples R China
[2] Sichuan Univ, W China Med Sch, Chengdu 610041, Sichuan, Peoples R China
[3] Third Mil Med Univ, Ctr Canc, Daping Hosp, Chongqing, Peoples R China
[4] Third Mil Med Univ, Inst Surg Res, Chongqing, Peoples R China
[5] Sichuan Univ, W China Hosp 2, Dept Gynecol & Obstet, Chengdu 610041, Sichuan, Peoples R China
关键词
apoptosis; colorectal carcinoma; polo-like kinase 1 (PLK1); RNA interference (RNAi); KINASE; 1; PHYSICAL INTERACTION; BREAST-CANCER; LUNG-CANCER; PLK1; EXPRESSION; POLO-LIKE-KINASE-1; MITOSIS; CELLS; PHOSPHORYLATION;
D O I
10.1089/cbr.2010.0922
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Polo-like kinase 1 (PLK1) showing a high expression in various kinds of tumors is considered a candidate target for cancer therapy. The aim of our study was to explore the effects of silencing PLK1 gene on human colorectal carcinoma cell line HCT-116 in vitro and in vivo. In vitro, the plasmids generating short hairpin RNA (shRNA)-targeting PLK1 were transfected into HCT-116 by using FugeneHD reagent, and the silencing potency was measured by RT-PCR, western blot, flow cytometry, and Caspase-Glo 3/7 assay, respectively. In vivo, the growth inhibition capacity of PLK1-shRNA on HCT-116 xenograft was measured in nude mice. Then, the silencing effect of PLK1 was analyzed by RT-PCR, western blot, and immunohistochemistry, respectively. Apoptosis, angiogenesis, and proliferation in tumor tissues were measured by TUNEL, CD31, and PCNA stain, respectively. The RNA interference targeting PLK1 significantly decreased the expression of PLK1 in vitro. More importantly, anti-PLK1 treatment in HCT-116 xenograft decreased tumor weight by 81.58% compared with the control group (p < 0.001), accompanied with decreased PLK1 mRNA and protein expression, increased cell apoptosis, and reduced angiogenesis and proliferation (p < 0.001). Our study showed that knockdown of PLK1 by shRNA might be the potential therapeutic approach against human colorectal carcinoma.
引用
收藏
页码:427 / 436
页数:10
相关论文
共 48 条
  • [1] Polo-like kinase 1 (Plk1) inhibits p53 function by physical interaction and phosphorylation
    Ando, K
    Ozaki, T
    Yamamoto, H
    Furuya, K
    Hosoda, M
    Hayashi, S
    Fukuzawa, M
    Nakagawara, A
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (24) : 25549 - 25561
  • [2] DECASTRO IP, 2007, CARCINOGENESIS, V28, P889
  • [3] Increased human polo-like kinase-1 expression in gliomas
    Dietzmann, K
    Kirches, E
    von Bossanyi, P
    Jachau, K
    Mawrin, C
    [J]. JOURNAL OF NEURO-ONCOLOGY, 2001, 53 (01) : 1 - 11
  • [4] Apoptosis induction with polo-like kinase-1 antisense phosphorothioate oligodeoxynucleotide of colon cancer cell line SW480
    Fan, Yu
    Zheng, Shu
    Xu, Ze-Feng
    Ding, Jia-Yi
    [J]. WORLD JOURNAL OF GASTROENTEROLOGY, 2005, 11 (29) : 4596 - 4599
  • [5] Off-target effects by siRNA can induce toxic phenotype
    Fedorov, Yuriy
    Anderson, Emily M.
    Birmingham, Amanda
    Reynolds, Angela
    Karpilow, Jon
    Robinson, Kathryn
    Leake, Devin
    Marshall, William S.
    Khvorova, Anastasia
    [J]. RNA, 2006, 12 (07) : 1188 - 1196
  • [6] A CONSERVED MITOTIC KINASE ACTIVE AT LATE ANAPHASE TELOPHASE IN SYNCYTIAL DROSOPHILA EMBRYOS
    FENTON, B
    GLOVER, DM
    [J]. NATURE, 1993, 363 (6430) : 637 - 640
  • [7] Influence of chk1 and plk1 silencing on radiation- or cisplatin-induced cytotoxicity in human malignant cells
    Gao, Qinglei
    Huang, Xiaoyuan
    Tang, Duozhuang
    Cao, Yang
    Chen, Gang
    Lu, Yunping
    Zhuang, Liang
    Wang, Shixuan
    Xu, Gang
    Zhou, Jianfeng
    Ma, Ding
    [J]. APOPTOSIS, 2006, 11 (10) : 1789 - 1800
  • [8] Polo-like kinases: a team that plays throughout mitosis
    Glover, DM
    Hagan, IM
    Tavares, AAM
    [J]. GENES & DEVELOPMENT, 1998, 12 (24) : 3777 - 3787
  • [9] RNA interference against viruses: strike and counterstrike
    Haasnoot, Joost
    Westerhout, Ellen M.
    Berkhout, Ben
    [J]. NATURE BIOTECHNOLOGY, 2007, 25 (12) : 1435 - 1443
  • [10] POLO-LIKE KINASE IS A CELL-CYCLE-REGULATED KINASE ACTIVATED DURING MITOSIS
    HAMANAKA, R
    SMITH, MR
    OCONNOR, PM
    MALOID, S
    MIHALIC, K
    SPIVAK, JL
    LONGO, DL
    FERRIS, DK
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (36) : 21086 - 21091